Our research program focuses on four subject areas: (1) the nature of malaria protection conferred to individuals by red blood cell (RBC) polymorphisms, including hemoglobin C, hemoglobin S, hemoglobin E, alpha-thalassemia and G6PD deficiency; (2) the parasite and host factors that influence the clearance of Plasmodium falciparum parasites in patients treated with the antimalarial drug artemisinin; (3) the molecular mechanisms of P. falciparum resistance to frontline antimalarial drugs, including artemisinin and piperaquine; and (4) the role of Anopheles mosquito vectors in the spread of multidrug-resistant P. falciparum parasites. In each of these areas we seek research advances that can improve the knowledge of disease processes and antimalarial drug resistance mechanisms in patients with malaria and thereby support the development of new antimalarial therapeutics, vaccines, and transmission-blocking interventions that aim to prevent illness and death. Our programs research activities are multidisciplinary and include multiple field sites in malarious regions of Mali and Cambodia as well as basic laboratory investigations at NIH-sponsored laboratories in these countries.